Influence of estradiol and triiodothyronine on breast cancer cell lines proliferation and expression of estrogen and thyroid hormone receptors

Cestari, Sílvia Helena; Figueiredo, Nancy Bueno; Conde, Sandro José; Clara, Sueli A.; Katayama, Maria Lúcia Hirata; Padovani, Carlos Roberto; Brentani, Maria Mitzi; Nogueira, Célia Regina

doi:10.1590/s0004-27302009000700010

Cited by 22 publications

(15 citation statements)

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“…The addition of T4 to BC-derived cell lines has been shown to increase cell proliferation [ 3 ], while in the presence of estrogen receptor (ER)-positive BC cell lines the addition of T3 inhibits cell proliferation [ 7 ]. These effects are important, as abnormalities in thyroid function tests have been observed in a variety of nonthyroidal illness, without preexisting thyroid or hypothalamic-pituitary disease, including BC [ 80 ].…”

Section: Discussionmentioning

confidence: 99%

Thyroid hormones and breast cancer association according to menopausal status and body mass index

et al. 2018

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BackgroundThyroxine (T4) has been positively associated with tumor cell proliferation, while the effect of triiodothyronine (T3) on cell proliferation has not been well-established because it differs according to the type of cell line used. In Mexico, it has been reported that 14.5% of adult women have some type of thyroid dysfunction and abnormalities in thyroid function tests have been observed in a variety of non-thyroidal illnesses, including breast cancer (BC). These abnormalities might change with body mass index (BMI) because thyroid hormones are involved in the regulation of various metabolic pathways and probably by menopausal status because obesity has been negatively associated with BC in premenopausal women and has been positively associated with BC in postmenopausal women.MethodsTo assess the association between serum thyroid hormone concentration (T4 and T3) and BC and the influence of obesity as an effect modifier of this relationship in premenopausal and postmenopausal women, we measured serum thyroid hormone and thyroid antibody levels in 682 patients with incident breast cancer (cases) and 731 controls, who participated in a population-based case-control study performed from 2004 to 2007 in three states of Mexico. We tested the association of total T4 (TT4) and total T3 (TT3) stratifying by menopausal status and body mass index (BMI), and adjusted for other health and demographic risk factors using logistic regressions models.ResultsHigher serum total T4 (TT4) concentrations were associated with BC in both premenopausal (odds ratio (OR) per standard deviation = 5.98, 95% CI 3.01–11.90) and postmenopausal women (OR per standard deviation = 2.81, 95% CI 2.17–3.65). In premenopausal women, the effect of TT4 decreased as BMI increased while the opposite was observed in postmenopausal women. The significance of the effect modification was marginal (p = 0.059) in postmenopausal women and was not significant in premenopausal women (p = 0.22). Lower TT3 concentrations were associated with BC in both premenopausal and postmenopausal women and no effect modification was observed.ConclusionsThere is a strong association between BC and serum concentrations of TT3 and TT4; this needs to be further investigated to understand why it happens and how important it is to consider these alterations in treatment.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-1017-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Thyroid hormones and breast cancer association according to menopausal status and body mass index

et al. 2018

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“…In MCF-7, an estrogen receptor positive breast cancer cell line, the proliferative effect of thyroid hormone is not only initiated through the combination with the thyroid hormone receptor, but also through the combination with the estrogen receptor [37]. There are specific mechanisms that explain why thyroid hormone stimulate cell proliferation in gastric cancer cells, the cyclin/cyclin-dependent kinase levels and activity are involved [11].…”

Section: Discussionmentioning

confidence: 99%

Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine

Huang

Jin

et al. 2013

BMC Cancer

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BackgroundThyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy.MethodsThyroid hormones and NTIS prevalence at initial diagnosis and during chemotherapy were analyzed in 685 breast diseases patients (369 breast cancer, 316 breast benign lesions). The influence of thyroid hormones on chemotherapeutic efficacy was evaluated by chemosensitization test, to compare chemotherapeutic efficacy between breast cancer cells with chemotherapeutics plus triiodothyronine (T3) and chemotherapeutics only.ResultsIn breast cancer, NTIS prevalence at the initial diagnosis was higher and increased during chemotherapy, but declined before the next chemotherapeutic course. Thyroid hormones decreased signigicantly during chemotherapy. T3 can enhance the chemosensitivity of MCF-7 to 5-Fu and taxol, with progression from G0-G1 phase to S phase. The similar chemosensitization role of T3 were found in MDA-MB-231. We compared chemotherapeutic efficacy among groups with different usage modes of T3, finding pretreatment with lower dose of T3, using higher dose of T3 together with 5-Fu or during chemotherapy with 5-Fu were all available to achieve chemosensitization, but pretreatment with lower dose of T3 until the end of chemotherapy may be a safer and more efficient therapy.ConclusionsTaken together, thyroid hormones decreasing during chemotherapy was found in lots of breast cancer patients. On the other hand, thyroid hormones can enhance the chemotherapeutic efficacy through gatherring tumor cells in actively proliferating stage, which may provide a new adjuvant therapy for breast cancer in furture, especially for those have hypothyroidism during chemotherapy.

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“…(27) observaram 23,5% de positividade nas pacientes com CaM, en quanto controles normais tiveram uma positividade de apenas 8%. Achados semelhantes foram publicados por do ERalfa semelhante em ambos os tratamentos (38). Linhagens MCF7, que expressam ERalfa e ERbeta, apresentaram hiperplasia na presença de E2 e T3 (18), indicando que a presença do receptor beta é importante para a progressão tumoral.…”

Section: Resultsunclassified

Perfil dos hormônios da tireoide em pacientes com câncer de mama em estado de menopausa

Conde

Luvizotto

Síbio

et al. 2012

Arq Bras Endocrinol Metab

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ReSUMOObjetivo: Verificar o perfil dos hormônios tireóideos (HTs) em pacientes pós-menopausa portadoras de carcinoma de mama (CaM). Sujeitos e métodos: Participaram 12 pacientes com CaM em estádio I ou II sem intervenções que pudessem interferir na progressão tumoral e um grupo controle com 18 pacientes em pós-menopausa sem CaM. Foram dosados os níveis séricos de anticorpo antitiroperoxidase (TPOAB), hormônio estimulante da tireoide (TSH), tiroxina livre (T4L), estradiol (E2), hormônio folículo estimulante (FSH) e hormônio luteinizante (LH) antes e após a cirurgia, e realizada a imunoistoquímica dos receptores de estrógeno (ER) e progesterona (PR). Resultados: Quatro pacientes com CaM apresentaram alterações do perfil hormonal tireoidiano: dois hipertireoidismo, um hipotireoidismo e positividade TPO-AB, todas com ER e PR positivos. Os níveis de TSH dessas pacientes não foram diferentes dos níveis encontrados no grupo controle (1,89 ± 1,56 vs. 2,86 ± 3,12 mUI/mL), porém os níveis de T4L nas pacientes com CaM foram estatisticamente maiores que o controle (1,83 ± 0,57 vs. 1,10 ± 0,20 ng/dL). Conclusão: Esses resultados reforçam a necessidade de avaliação do status tireoidiano em pacientes com CaM, uma vez que, na ausência de E2, mudanças clínicas nos HTs podem atuar em vias controladas pelo E2. Arq Bras Endocrinol Metab. 2012;56(4):238-43 Descritores Hormônios tireóideos; neoplasias da mama; hipertireoidismo; pós-menopausa ABSTRACT Objective: The aim of this study was to determine thyroid hormone (TH) profile in postmenopausal patients with breast cancer (BC). Subjects and methods: 12 CaM patients stages I or II, without interventions that could interfere with tumor progression were selected, as well as and a control group with 18 postmenopausal women without CaM. We measured serum anti--thyroperoxidase antibody (TPOAB), thyroid-stimulating hormone (TSH), free thyroxine (T4L), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), before and after surgery, besides immunohistochemistry for estrogen (ER) and progesterone (PR) receptors. Results: Four patients with CaM showed changes in thyroid hormone profile: two had hyperthyroidism, one hypothyroidism, and one was positive for TPO-AB. All of them positive for ER and PR. TSH levels in breast cancer patients were not different from levels found in the control group (1.89 ± 1.56 vs. 2.86 ± 3.12 mIU/mL), but the levels of T4L in patients with CaM were statistically higher than those of the control group (1.83 ± 0.57 vs. 1.10 ± 0.20 ng/dL). Conclusion: These results reinforce the need for assessment of thyroid status in CaM patients, since in the absence of E2, changes in clinical HTs can act in E2-controlled processes. Arq Bras Endocrinol Metab. 2012;56(4):238-43

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Influence of estradiol and triiodothyronine on breast cancer cell lines proliferation and expression of estrogen and thyroid hormone receptors

Cited by 22 publications

References 27 publications

Thyroid hormones and breast cancer association according to menopausal status and body mass index

Thyroid hormones and breast cancer association according to menopausal status and body mass index

Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine

Perfil dos hormônios da tireoide em pacientes com câncer de mama em estado de menopausa

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